Effects of Physical Activity on DNA Methylation and Associations with Breast Cancer

Abstract

Physical activity is associated with reduced breast cancer risk and improved disease outcome. Initial research indicates that physical activity can lower circulating levels of sex steroid hormones, improve insulin resistance, and reduce mitogenic growth factors. Recent investigation suggests that physical activity may have more profound impact on epigenetic regulation. As a key component of epigenetic regulation, DNA methylation has been found to be altered by physical activity. Physical activity may reduce DNA methylation in tumor suppressor genes and increase methylation in the genes encoding pro-inflammatory cytokines. Studies also suggest that physical activity may change the landscape of DNA methylation by increasing genome-wide methylation. These characteristic changes in DNA methylation are also observed in experimental studies in which healthy individuals or breast cancer patients with increased physical activity had significantly reduced DNA methylation in tumor suppressor genes and elevated methylation in the entire genome. All these molecular changes are consistent with the observations that physical activity is associated with low cancer risk and better patient survival, which explains the molecular mechanisms that underlie the beneficial effects of physical activity on cancer prevention and management.